title: Apolipoprotein E and lipoprotein lipase secreted from human monocyte-derived macrophages modulate very low density lipoprotein uptake.
abstract: We investigated the roles of lipoprotein lipase and apolipoprotein E (apoE) secreted from human monocyte-derived macrophages in the uptake of very low density lipoproteins (VLDL). ApoCII-deficient VLDL were isolated from a patient with apoCII deficiency. The lipolytic conversion to higher density and the degradation of the apoCII-deficient VLDL by macrophages were very slight, whereas the addition of apoCII enhanced both their conversion and degradation. This suggests that the lipolysis and subsequent conversion of VLDL to lipoproteins of higher density are essential for the VLDL uptake by macrophages. VLDL incubated with macrophages obtained from subjects with E3/3 phenotype (E3/3-macrophages) showed a 17-fold greater affinity in inhibiting the binding of 2 micrograms/ml 125I-low density lipoprotein (LDL) to fibroblasts than native VLDL, whereas the incubation of VLDL with macrophages obtained from a subject with E2/2 phenotype (E2/2-macrophages) did not cause any increase in their affinity. Furthermore, 3 micrograms/ml 125I-VLDL obtained from a subject with E3/3 phenotype were degraded by E3/3-macrophages to a greater extent than by E2/2-macrophages (2-fold), indicating that VLDL uptake is influenced by the phenotype of apoE secreted by macrophages. From these results, we conclude that both lipolysis by lipoprotein lipase and incorporation of apoE secreted from macrophages alter the affinity of VLDL for the LDL receptors on the cells, resulting in facilitation of their receptor-mediated endocytosis.
authors.affiliation: Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ishibashi
authors.forename: N
authors.initials: N
authors.lastname: Yamada
authors.forename: H
authors.initials: H
authors.lastname: Shimano
authors.forename: N
authors.initials: N
authors.lastname: Mori
authors.forename: H
authors.initials: H
authors.lastname: Mokuno
authors.forename: T
authors.initials: T
authors.lastname: Gotohda
authors.forename: M
authors.initials: M
authors.lastname: Kawakami
authors.forename: T
authors.initials: T
authors.lastname: Murase
authors.forename: F
authors.initials: F
authors.lastname: Takaku
mesh_terms: D053304:Apolipoprotein C-II; D001056:Apolipoproteins C / Q000097:blood / Q000172:deficiency; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D006952:Hyperlipoproteinemia Type III / Q000097:blood; D007223:Infant; D007700:Kinetics; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008074:Lipoproteins / Q000097:blood* / Q000302:isolation & purification; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D010641:Phenotype; D012016:Reference Values; D012867:Skin / Q000378:metabolism
chemical_list: D053304:Apolipoprotein C-II; D001056:Apolipoproteins C; D001057:Apolipoproteins E; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D008071:Lipoprotein Lipase